Aim:Depression is one of the most common psychological disorders in end-stage renal disease (ESRD) patients and is associated with impaired quality of life and increased mortality and rate of hospitalization. We aimed to examine the contributions of depression and the use of antidepressive agents in the mortality of ESRD patients. Methods: A retrospective observatory study was conducted using the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed as ESRD during the year 2001 to 2007 were collected. A total of 2312 ESRD patients were identified in the database. Statistical analyses were conducted to examine the contributions of depression and exposure of antidepressive agents in mortality rates of ESRD patients. Results:Diagnosis of depression did not influence mortality rate (mortality rate in patients with depression: 26.5%; mortality rate in patients without depression: 26.2%; P= 1.000). Those who had antidepressive agents exposure had significantly higher mortality rate (mortality rate: 32.3%) than those who did not (mortality rate: 24.5%) (P < 0.001). Conclusions: Our findings suggest that (i) the mortality rate of ESRD patients was not affected by the diagnosis of depression, and (ii) exposure of antidepressive agents in ESRD patients was associated with a higher mortality rate. The high mortality rate in ESRD patients exposed to antidepressive agents can be a bias by indication. Equally, a true contribution of the antidepressive agents cannot be ruled out and this needs clarification.